Subscribe to this blog

Follow by Email

This is a modified version of a letter
published in Trends in Genetics: Kevin J. Mitchell (2012). Genetic entropy
and the human intellect. Trends in Genetics, 14th December 2012.

Two articles by Gerald Crabtree float the
notion that we, as a species, are gradually declining in average intellect, due
to the accumulation of mutations that deleteriously affect brain development or
function [1, 2]. The
observations that prompted this view seem to be: (i) intellectual disability
can be caused by mutations in any one of a very large number of genes, and: (ii)
de novo mutations arise at a low but
steady rate in every new egg or sperm. He further proposes that: (iii) genes
involved in brain development or function are especially vulnerable to the
effects of such mutations. Considered in isolation, these could reasonably lead
to the conclusion that mutations reducing intelligence must be constantly
accumulating in the human gene pool. Thankfully, these factors do not act in
isolation.

If we, as a species, were simply constantly
accumulating new mutations, then one would predict the gradual degradation of every
aspect of fitness over time, not just intelligence. Indeed, life could simply not
be sustained over evolutionary time in the face of such genetic entropy. Fortunately
– for the species, though not for all individual members – natural selection is
an attentive minder.

Analyses of whole-genome sequences from
large numbers of individuals demonstrate an “excess” of rare or very rare
mutations [3, 4]. That
is, mutations that might otherwise be expected to be at higher frequency are
actually observed only at low frequency. The strong inference is that selection
is acting, extremely efficiently, on many mutations in the population to keep
them at a very low frequency.

One of the key misconceptions in the
Crabtree articles is that mutations happen to “us”, as a species. His
back-of-the-envelope calculations lead him to the following conclusions: “Every 20-50 generations we should sustain a
mutation in one copy of one of our many ID [intellectual deficiency] genes. In
the past 3000 years then (~120 generations), each of us should have accumulated
at the very least 2.5-6 mutations in ID genes”.

The loose phrasing of these sentences
reveals a fundamental underlying fallacy. “We” have not sustained mutations in
“our” ID genes, and “each of us” has not accumulated anything over the past
3000 years, having only existed for a fraction of that. Mutations arise in
individuals, not populations. Nor does it matter that there are many thousands
of genes involved in the developmental systems that generate a well-functioning
human brain – selection can very effectively act, in individuals, on new
mutations that impair these systems.

Mutations causing intellectual disability
dramatically impair fitness, explaining why so many cases are caused by de novo mutations – the effects are often
too severe for them to be inherited [5]. Furthermore, this selective pressure extends into the normal range
of intelligence, as described by Deary: “One
standard deviation advantage in intelligence was associated with 24% lower risk
of death over a follow-up range of 17 to 69 years… The range of causes of
death with which intelligence is significantly associated… include deaths from
cardiovascular disease, suicide, homicide, and accidents”[6].

A more recent study of over 1 million
Swedish men found that lower IQ in early adulthood was also associated with
increased risk of unintentional injury.“After adjusting for confounding
variables, lower IQ scores were associated with an elevated risk of any unintentional
injury (Hazard ratio per standard deviation decrease in IQ: 1.15), and of
cause-specific injuries other than drowning (poisoning (1.53), fire (1.36), road
traffic accidents (1.25), medical complications (1.20), and falling (1.17).
These gradients were stepwise across the full IQ range”. None of that sounds good.

Crabtree suggests, however, that brains and
intelligence are special cases when it comes to the effects of genetic
variation and natural selection. First, he argues that ID genes are members of
a chain, where every link is fragile, rather than of a robust network. This
view is mistaken, however, as it ignores all the genes in which mutations do
not cause ID – this is the robust network in which ID genes are embedded. He
also cites several studies reporting high rates of retrotransposition (jumping around of mobile DNA elements derived from retroviruses) and
aneuploidy (change in chromosome number) in neurons in human brains. He argues that these processes of
somatic mutation would make brain cells especially susceptible to loss of heterozygosity, as an inherited mutation in one copy of a gene might be
followed by loss of the remaining functional copy in many cells in the brain.

If these reports are accurate, such processes
would indeed exacerbate the phenotypic consequences of germline mutations, but
this would only make them even more visible to selection. However, it seems
unlikely, a piori, that these mechanisms play an important role. First, it
would seem bizarre that evolution would go to such lengths to craft a finely
honed human genome over millions of years only to let all hell break loose in what
Woody Allen calls his second favourite organ. One would predict, in fact, that
if such mechanisms really prevailed we would all be riddled with brain cancer.
In addition, if these processes had a large effect on intelligence in
individuals, this would dramatically reduce the heritability of the trait
(which estimates the contribution of only inherited genetic variants to
variance in the trait). The fact that the heritability of IQ is extremely high
(estimated between ~0.7 to 0.8) suggests these are not important mechanisms [6]. This view is directly reinforced by a recent study by Chris Walsh
and colleagues, who, using the more direct method of sequencing of the entire
genomes of hundreds of individual human neurons, found vanishingly low rates of
retrotransposition and aneuploidy [7].

Crabtree additionally suggests that modern
societies shelter humans from the full scrutiny of natural selection,
permitting dullards to thrive and deleterious mutations to accumulate. He
speculates that high intelligence would have been more important in
hunter-gatherer societies than in more modern societies that arose with
high-density living. No evidence is offered for this idea, which contradicts
models suggesting just the opposite – that the complexities of social
interactions in human societies were actually a main driver of increasing
intelligence [8]. Indeed, over the past millennium at least, there is evidence of a strong
association between economic success (itself correlated with intelligence) and
number of surviving children, suggesting selection on intelligence at least up
until very recent times. In contrast, number of offspring in contemporary hunter-gatherer
societies has been linked more to aggression and physical prowess [9].

Arguments that reduced intelligence does
not impair fitness in modern societies can thus be directly refuted. But there
is another way to think about this association, which considers intelligence
from a very different angle [10]. Rather than a dedicated cognitive faculty affected by variation in
genes specifically “for intelligence”, or, conversely, degraded by mutations
genes “for intellectual disability”, intelligence may actually be a
non-specific indicator of general fitness. In this scenario, the general load
of deleterious mutations in an individual cumulatively impairs phenotypic
robustness or developmental stability – the ability of the genome to direct a
robust program of development, including development of the brain. Reduced
developmental stability will affect multiple physiological parameters,
intelligence being just one of them [11].

This model is supported by observed
correlations between intelligence and measures of developmental stability, such
as minor physical anomalies and fluctuating asymmetry (a more robust
developmental program generating a more symmetric organism) [12]. Intelligence is also correlated with diverse physical and mental health
outcomes, from cardiovascular to psychiatric disease [6]. Under this model, intelligence gets a free ride. It is maintained
not by selection on the trait itself, but on the coat-tails of selection
against mutational load generally.

Whether causally or as a correlated
indicator, intelligence is thus strongly associated with evolutionary fitness,
even in current societies. The threat posed by new mutations to the intellect
of the species is therefore kept in check by the constant vigilance of
selection. Thus, despite ready counter-examples from nightly newscasts, there
is no scientific reason to think we humans are on an inevitable genetic
trajectory towards idiocy.

Comments

Interesting article. This is relevant to the movie "Idiocracy." However, you are using death rates as a proxy for which genes will be selected out of the population. Your assumption is that reproduction rates are otherwise independent of intelligence. In fact, most studies seem to show a negative correlation between fecundity and IQ: http://en.wikipedia.org/wiki/Fertility_and_intelligence#Later_research. Probably is a small effect, could be confounded by SES/transgenerational epigenetic inheritance, and likely won't matter as long as education and environmental stimulation continue to improve. Plus AI. But still, worth pointing out.

Thanks Andy. You are absolutely right that I did not consider possible tradeoffs in fitness based on increased fecundity associated with lower IQ. This may hold in some current societies. (Possibly more for generation time than number of children per se). I did not discuss it because the original article's claims relate to changes in selection pressures across evolutionary time (or at least thousands of years), rather than differences across social strata in current societies.

In all seriousness, I know of three families with many offspring who appear to be mentally impaired. In one there is a strong history of dementia, in another there seems to be a gene that makes them unusually tall and stupid, and in the other there's a combination of bad genetic and environmental influences. Families like these must have some kind of impact on the overall picture.

Now days Business PBX come packed with a lot of features. You can basically customize your business PBX to fit your business needs. When you see the features, you will know how your current phone system is not good enough. I have been using hosted pbx from Telcan. With this business PBX, I can customize the welcome greeting, route calls to multiple numbers, even program what phone number to call at what time, have a professional voicemail, get my voicemail emailed and the list goes on. It is very easy to set up using wizard. Check out PBX

Small Business Phone Service is a cost-efficient alternative to premise based phone systems. Small business virtual PBX phone system is of great utility value in offices. PBX phone systems for small businesses help save huge capital expenditure as well as increase business productivity.

Post a Comment

Popular posts from this blog

Can molecular memories of our ancestors’
experiences affect our own behaviour and physiology? That idea has certainly
grabbed hold of the public imagination, under the banner of the seemingly
ubiquitous buzzword “epigenetics”. Transgenerational epigenetic inheritance is
the idea that a person’s experiences can somehow mark their genomes in ways
that are passed on to their children and grandchildren. Those marks on the
genome are then thought to influence gene expression and affect the behaviour
and physiology of people who inherit them. The way this notion is referred to – both in
popular pieces and in the scientific literature – you’d be forgiven for
thinking it is an established fact in humans, based on mountains of consistent,
compelling evidence. In fact, the opposite is true – it is based on the
flimsiest of evidence from a very small number of studies with very small
sample sizes and serious methodological flaws. [Note that there is, by contrast,
very good evidence for this kind…

I recently wrote a blogpost examining the
supposed evidence for transgenerational epigenetic inheritance (TGEI) in
humans. This focused specifically on a set of studies commonly cited as
convincingly demonstrating the phenomenon whereby the experiences of one
generation can have effects that are transmitted, through non-genetic means, to
their offspring, and, more importantly, even to their grandchildren. Having
examined what I considered to be the most prominent papers making these claims,
I concluded that they do not in fact provide any evidence supporting that idea,
as they are riddled with fatal methodological flaws. While the scope of that piece was limited
to studies in humans, I have also previously considered animal studies making
similar claims, which suffer from similar methodological flaws (here and here).
My overall conclusion is that there is effectively no evidence for TGEI in
humans (contrary to widespread belief) and very little in mammals more
generally (with one very…

GWAS (genome-wide association studies) for
psychiatric illnesses may be about to become a victim of their own success. The
idea behind these studies is that common genetic variation – ancient mutations
that segregate in the population – may partly underlie the high heritability of
common psychiatric and neurological disorders, such as schizophrenia, autism,
epilepsy, ADHD, depression, and so on. The accumulating evidence from over ten
years of GWAS strongly supports that idea, with many hundreds of such risk
variants now having been identified. The problem is it’s not at all clear what
to do with that information. GWAS are a method to carry out a kind of
genetic epidemiology, based on a simple premise – if a particular genetic
variant at some position in the genome (say an “A” base, as opposed to a “T” at position 236,456 on chromosome 9) – is associated with an increased risk
of some condition, then the frequency of the “A” version should be higher in
people with the condition than pe…